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2106 Outcomes for Acute Myeloid Leukemia Relapse after Allogeneic Hematopoietic Cell Transplantation Remain Poor in the Modern Era

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster I
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Biological therapies, Antibody Therapy, adult, Checkpoint Inhibitor, Diseases, Therapies, Immunotherapy, Adverse Events, Myeloid Malignancies, Study Population, Human, Transplantation
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Shona Philip, MD1, Robert Lowsky, MD1, Laura J. Johnston, MD1, Sally Arai, MD2, Everett H Meyer, MD, PhD1*, Robert S. Negrin, MD1, Andrew R. Rezvani, MD3, Parveen Shiraz, MD1, Judith A Shizuru, MD, PhD4, Surbhi Sidana, MD5, Wen-Kai Weng, MD, PhD6, Sushma Bharadwaj, MD, MS4*, Matthew J Frank, MD, PhD7, David B. Miklos, MD, PhD1, Melody Smith, MD, MS8, Lori Muffly, MD4 and Vaibhav Agrawal, MD9

1Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA
2Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University Medical Center, Stanford, CA
3Stanford University School of Medicine, Stanford
4Division of BMT and Cellular Therapy, Stanford University, Stanford, CA
5Division of BMT and Cell Therapy, Stanford University Hospital, Stanford, CA
6Stanford Univ. School of Med., Stanford, CA
7Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA
8Adult Bone Marrow Transplant Service and Cellular Therapeutics Center, Stanford University, Stanford, CA
9Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA

Background: Relapse of acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation (allo-HCT) has historically been associated with dismal prognosis with most patients failing to achieve subsequent remission and estimated 2-year overall survival (OS) of <15 %. Rapid progress in the understanding of AML biology and genomics resulted in recent FDA approval of several novel small molecules and immunotherapies for the treatment of front-line and relapsed/refractory AML, as early as 2017. We hypothesized that the availability of novel therapies for AML relapsing after allo-HCT has resulted in an improved OS in recent years.

Methods: Patients with AML ≥18 years old who underwent allo-HCT at Stanford University between the years 2010 and 2021 and subsequently relapsed were included in this study. Patients were divided into two eras based on year of relapse: 2010-2016 (early era) and 2017- 2022 (later era). Descriptive statistics were used to characterize patients across the two cohorts; Kaplan Meier method was used to evaluate OS.

Results: A total of 258 adults with AML relapsed following allo-HCT; 142 (55%) transplanted in the early era and 116 (45%) in the later era. Relative to the early era, patients who relapsed in the later era were more likely to be Hispanic (19.8% vs. 8.5%, P=0.01), have adverse risk leukemia (64.7% vs 52.1%, P=0.039), poorer performance status as defined by KPS <90 (46.6% vs. 16.9%, p<0.001), an HCT-comorbidity index of ≥ 3 (43.1% vs. 28.2%, P=0.012), and receive alternative donor transplant (haploidentical donors 11.2% vs 3.5%, P=0.002; umbilical cord blood 9.5% vs. 4.2%, P=0.002). Post-HCT maintenance therapy was used more frequently in the later era (16.4% vs. 2.1%, P=0.002). Median age, sex, and conditioning intensity did not significantly differ between the two cohorts.

The median time to AML relapse post-HCT was similar in the early vs late era (149 days vs. 172 days, P=0.003). The management of relapse differed significantly across eras (Figure 1), as expected, with patients in the later era more commonly receiving targeted therapy with FLT3 inhibitors and IDH1/2 inhibitors (25% vs. 7.7%), hypomethylating agents (HMA) (51.7% vs. 35.2%) and BCL2 inhibitors (32.8% vs 3.5%) and less likely receiving cytotoxic chemotherapy (21.6% vs 34.5%). The use of donor lymphocyte infusion increased over time (16.9% vs. 12.1%) as did second allo-HCT (10.3% vs. 7%).

Despite increased use of novel therapies in the later era, there was no improvement in median OS compared to the early era (5.1 months versus 4.5 months, p=0.43) or 2-year OS following post-HCT relapse (19.1% vs. 12.4%, P=0.26), (Figure 2). Across both eras, relapsed AML was the most common cause of death in this cohort, attributed to 83.7% of all deaths.

Conclusion: Despite the greater use of novel therapies to treat post-HCT relapse of AML in recent years, OS remains poor and has not improved. Relapsed AML following allo-HCT remains a significant clinical challenge despite advances in modern AML therapeutics.

Disclosures: Lowsky: Orca Bio: Research Funding. Arai: Kadmon: Membership on an entity's Board of Directors or advisory committees. Meyer: indee labs: Membership on an entity's Board of Directors or advisory committees; Orca Bio: Research Funding; GigaGen: Other: Co-founder, scientific advisor; Triursus Therapeutics: Other: Co-founder, scientific advisor. Negrin: CoImmune: Current equity holder in private company, Current holder of stock options in a privately-held company; University of Pennsylvania: Other: DSMB or Advisory Board; Novartis: Consultancy; UptoDate: Honoraria; Amgen: Consultancy; Kuur: Consultancy; Garuda: Consultancy; Magenta: Consultancy, Current equity holder in publicly-traded company; BioEclipse Therapeutics: Current equity holder in private company, Current holder of stock options in a privately-held company. Shiraz: Kite, a Gilead company: Research Funding. Shizuru: Jasper Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; rBio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Shoreline BioSciences: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Sidana: Prothena: Honoraria; Magenta Therapeutics: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Allogene: Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy. Frank: Roche/Genentech - Wife: Current equity holder in private company, Current holder of stock options in a privately-held company; Allogene Therapeutics: Research Funding; Kite/Gilead: Honoraria, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Research Funding. Miklos: Fosun Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite, a Gilead Company: Research Funding; Adaptive Biotech: Consultancy; Bristol Meyers Squibb: Consultancy; Novartis: Consultancy; Allogene: Research Funding; Pharmacyclics: Patents & Royalties: cGVHD Ibrutinib patent . Muffly: Kite: Consultancy, Research Funding; Jasper: Research Funding; BMS: Research Funding; Astellas: Consultancy, Research Funding; Adaptive: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Consultancy; Medexus: Consultancy; CTI Biopharma: Consultancy.

*signifies non-member of ASH